1. Field of the Invention
The present invention relates to a novel anti-mucin 1 protein antibody and a reagent for immunoassay containing the same. The present invention also relates to a reagent and a method for determining a disease or disorder associated with human mucin 1 protein.
2. Background Art
Gastric cancer is a frequent cancer, ranking first for males and second for females in the frequency of Japanese morbidity of malignant tumors; internationally, many patients with gastric cancer are present in Asia such as China, Japan, and Korea and South America. Even in these days of advanced diagnostic imaging and endoscopy, the number of deaths from gastric cancer was 49,535 (32,142 for males and 17,393 for females) in Japan in 2003, and gastric cancer was second only to lung cancer for males and second only to colon cancer for females in that number (from the Population Survey Report conducted by the Health the Labour and Welfare Ministry, Japan).
Among various tissue types of gastric cancer, “poorly differentiated adenocarcinoma: non-solid type” (abbr. “por2”) and “signet-ring cell carcinoma” (abbr. “sig”) are of particularly high malignancy and also often have the state of “scirrhous gastric cancer,” many cases of which have already been in the situation of “being too late” when detected and which corresponds to “type 4” for the macroscopic tumor.
“Scirrhous gastric cancer” is the most malignant cancer among gastric cancers and occurs in the mucosa like other gastric cancers; however, it has the characteristic of widely spreading in the stomach wall while not causing prominent change in the mucosal surface. “Scirrhous gastric cancer” accounts for about 10% of all gastric cancers, is often found in the young generations in their thirties and forties, and is hard to be diagnosed even by specialists; about 60% of such patients have already had peritoneal metastasis or broad lymph node metastasis at the time of detection, and it is often the case that cancer has already progressed when recognized by complaints of anxiety about the physical condition. Even if the cancer can be removed by surgery, it has high recurrence rate. The metastasis typical of “scirrhous gastric cancer” is peritoneal dissemination, which occurs in about one-half of individuals affected by cancer of this type.
The final definite diagnosis of gastric cancer is performed by the histopathological diagnosis of a biopsy specimen under endoscopy; however, the common hematoxylin-eosin (HE) staining of gastric biopsy tissue is at a high risk of “detection failure of cancer” because cancer cells are often among proliferated granulation tissue and fibrous tissue and difficult to determine where the cancer cells are. To prevent detection failure of cancer, some pathological test facilities perform periodic acid-Schiff stain (PAS stain) as a specific stain in all gastric biopsy specimens. However, the PAS stain also often fails to identify gastric cancer cells because it also stains non-cancer substances such as inflammatory cells frequently present around the gastric cancer cells. “Detection failure of cancer” must be avoided by all means particularly in a gastric biopsy specimen of a case suspected of “scirrhous gastric cancer” which is clinically difficult to diagnose.
As described above, the accurate histopathological diagnosis of “poorly differentiated adenocarcinoma: non-solid type (por2)” or “signet-ring cell carcinoma (sig)” having a strong tendency to become “scirrhous gastric cancer” is extremely effective in the early detection of “scirrhous gastric cancer” and essential for improving the outcome of gastric cancer treatment. For the histopathological diagnosis, the need for immunostaining based on a protein or sugar chain specifically expressed in pathological tissue of gastric cancer becomes increasingly important, and the development competition of an antibody therefore is being intensified.
Mucin-type glycoproteins are mucous substances contained in the mucus for protecting the mucosa of the intestinal tract, respiratory tract, oral cavity, uterus, etc. in the animals, and are proteins having many sugar chains (called mucin-type sugar chains). For human, 18 types are reported as those of mucin (MUC) genes encoding such proteins; 11 types thereof encode transmembrane-type proteins and 7 types encode secretory-type proteins. The mucin genes are reported to be associated with various diseases, for example, cancer, inflammatory bowel disease, asthma, and the like. For example, the expression of mucin 1 (MUC1) has been shown to be associated with the poor prognosis of patients with various human cancers (pancreatic cancer, bile duct cancer, gastric cancer, esophageal cancer, breast cancer, lung cancer, and the like) (Yonezawa S, Goto M. Yamada N, Higashi M, Nomoto M: Expression profiles of MUC1, MUC2 and MUC4 mucins in human neoplasms and their relationship with biological behavior. Proteomics 8 (16): 3329-3341, 2008).
MUC1 was earliest cloned among mucin antigens considered dominant as tumor markers, and the number of antibodies against MUC1 is now more than 400. For example, there are reported an antibody recognizing and reacting with a sugar chain present in the tandem repeat of the extracellular region of the MUC1 protein and an antibody recognizing and reacting with amino acids 1,110 to 1,155 (45 amino acids) corresponding to the C-terminal side of the cleavage sate at the extracellular region thereof (Mahanta S, et al.: PLoS ONE vol 3. Issue 4. e2054, 2008). However, as described above, there has remained a need for the development of an antibody capable of sensitively and simply detecting cancer cells of poorly differentiated adenocarcinoma or signet-ring cell carcinoma which has particularly high malignancy among gastric cancers, is difficult to find out by diagnostic imaging or endoscopy, and is at a high risk of detection failure by usual hematoxylin-eosin (HE) staining even in the pathological diagnosis of gastric biopsy tissue providing the final diagnosis.